Abstract Rationale Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. In WAYPOINT (NCT04851964), tezepelumab significantly reduced nasal polyp (NP) size and improved sino-nasal symptoms versus placebo in adults with severe chronic rhinosinusitis with NP (CRSwNP). This post hoc analysis evaluated the effect of tezepelumab on type 2 (T2) inflammatory biomarker levels in nasal lining fluid (NLF) and clinical outcomes among patients with comorbid asthma from WAYPOINT. Methods WAYPOINT was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults (aged ≥18 years) with severe CRSwNP (61% with reported comorbid asthma) were randomized (1:1) to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. This analysis explored the change from baseline to weeks 24 and 52 in NLF interleukin (IL)-5 and IL-13 levels and relationships between baseline NLF cytokine levels and total NP and nasal congestion score at week 52. Results Overall, 345 patients were included in this analysis (tezepelumab, n = 174 comorbid asthma, n = 109; placebo, n = 171 comorbid asthma, n = 108). The least-squares mean (95% confidence interval CI) reductions in NLF IL-5 and IL-13 levels for tezepelumab versus placebo at week 52 were 90.4% (85.0%, 93.8%) and 93.1% (89.9%, 95.3%), respectively. Participants with comorbid asthma had higher median baseline levels of NLF IL-5 (16.0 vs 5.9 pg/mL) and IL-13 (91.0 vs 19.0 pg/mL) than those without comorbid asthma. For those with and without comorbid asthma, mean (95% CI) reductions in IL-5 at week 24 were 94.2% (90.0%, 96.6%) and 83.6% (67.6%, 91.7%), respectively, whereas reductions in IL-13 were 94.8% (91.5%, 96.9%) and 86.9% (75.1%, 93.1%), respectively. For those with and without comorbid asthma, reductions in IL-5 at week 52 were 90.4% (83.1%, 94.6%) and 90.1% (79.8%, 95.2%), respectively, and reductions in IL-13 were 94.0% (90.2%, 96.3%) and 91.2% (83.6%, 95.3%), respectively. In both groups, improvements in clinical outcomes at week 52 were more pronounced among patients with cytokine levels at or above the median at baseline (Figure). Conclusions This novel analysis shows that patients with CRSwNP and comorbid asthma have higher expression of NLF T2 cytokines at baseline than those without asthma, and tezepelumab reduced cytokine levels in both groups. Tezepelumab significantly improved clinical responses across subgroups, with numerically greater improvements in patients with CRSwNP and comorbid asthma versus without asthma or with higher versus lower baseline NLF T2 cytokine levels. These results support the benefits of tezepelumab treatment in CRSwNP with and without comorbid asthma. This abstract is funded by: AstraZeneca
Lipworth et al. (Fri,) studied this question.